1000 GMT July 21, 2018
Inter is 12th in the Serie A table after a 1-0 loss at Sampdoria on Sunday, its fourth defeat in five league games, BBC reported.
Former Netherlands defender and ex-Ajax boss De Boer, 46, was heavily linked with vacancies at Premier League clubs Everton and Southampton in the summer.
Inter visits Southampton in the Europa League on Thursday (20:05 GMT).
Youth team coach Stefano Vecchi will take charge of the first team for that fixture.
De Boer tweeted that "to carry out this project needed more time" and thanked Inter supporters for their support.
Before joining Inter, De Boer had taken Ajax to four successive Dutch titles but lost out to PSV Eindhoven on the final day of last season.
He signed a three-year contract with Inter in August, replacing former Manchester City manager Roberto Mancini.
It is six years since Inter won the treble of Serie A, Coppa Italia and Champions League under Jose Mourinho — now Manchester United boss — but since coming second in 2011 it has finished sixth, ninth, fifth, eighth and fourth.
It is now looking for a ninth manager since Mourinho left in the summer of 2010.
Newcastle boss Rafael Benitez, Leicester manager Claudio Ranieri and Watford boss Walter Mazzarri have all coached at the San Siro in the past six years.